Pubertal Maturation and Motivational Influences on Frontolimbic Systems

描述(由申请者提供)：在理解青春期如何影响支持情绪调节的典型青少年的神经系统方面，存在着根本的差距。填补这一空白对于增进对情绪障碍风险的神经发育标志物的了解很重要，情绪障碍通常在青春期发病，特别是在女孩中。 长期目标是了解额叶边缘-纹状体系统的发展，以阐明情绪障碍风险的生物标记物，以及可塑性增强的时期，为基于大脑的有针对性的神经行为干预提供信息。鉴于注意偏向在情绪障碍中的重要性，这一特定应用的目的是更深入地了解青春期对在情绪刺激背景下负责注意力控制的额缘系统的影响，以及青春期对奖励系统的影响可以在多大程度上支持刺激的效果，以加强注意控制过程。中心假设是青春期成熟伴随性激素水平升高，影响前额叶控制和皮质下控制的神经活动和功能连接。 边缘区域对目标无关背景下注意力控制能力的影响 情感刺激。同时，它们也影响额纹状体系统的活动 提高奖励的敏感度，促进激励性学习。这项拟议研究的基本原理是，了解青春期额叶-边缘-纹状体系统的发育，有可能转化为对情绪障碍风险的机械性理解，目前，在任何给定的时间，大约每10名年轻人中就有一人患有这种疾病，而且还可以创造出创新的发展敏感干预措施。其具体目标是：1)在健康青少年中确定青春期如何影响情绪刺激背景下支持注意控制的神经区中的神经活动和神经区域之间的功能连接；2)在健康青少年中确定青春期对奖励系统的影响在多大程度上将在情绪刺激背景下加强注意控制的回报调节。探索性分析将研究青春期对大脑结构的影响，以及青春期期间神经指数的变化如何与情绪症状水平的变化相关。一项纵向设计将被用来通过招募年龄匹配但青春期状态不同的男性和女性来区分Pubety-vs.年龄相关的影响。性激素水平将被测量，以确定青春期成熟的个体差异。将使用fMRI情绪工作记忆范式(在有或没有激励的情况下)来探索额叶边缘功能，该范式已知招募参与注意力控制的前额叶皮质区域，以及与情绪处理相关的皮质下边缘区域。这种方法是创新的，因为它检查了青春期对与情绪调节有关的额叶边缘-纹状体系统的特定影响。这项拟议的研究意义重大，因为它可以导致识别情绪障碍风险的神经标记物，并为未来的干预研究提供信息，这些研究基于发育神经科学的知识。

DESCRIPTION (provided by applicant): There is a fundamental gap in understanding how puberty affects neural systems supporting emotion regulation in typically developing adolescents. Filling this gap is important to advance knowledge regarding neurodevelopmental markers of risk for mood disorders, which typically onset during adolescence particularly in girls. The long-term goal is to understand the development of frontolimbic-striatal systems in order to elucidate bio- markers of risk for mood disorders as well as periods of heightened plasticity to inform targeted brain-based neurobehavioral interventions. Given the importance of attentional biases in mood disorders, the objective in this particular application is to gain a deeper understanding of puberty-specific effects on frontolimbic systems responsible for attentional control in the context of emotional stimuli and the extent to which pubertal influences on reward systems can bolster the effects of incentives to enhance attentional control processes. The central hypothesis is that pubertal maturation coupled with elevated levels of sex hormones influence neural activity in and functional connectivity between prefrontal control and subcortical limbic regions contributing to a reduction in attentional control in the context of goal-irrelevant emotional stimuli. In parallel, they also influence activity in frontostriatal systems in ways that heighten sensitivity to reward and promote incentive-based learning. The rationale for the proposed research is that understanding the development of fronto-limbic-striatal systems during adolescence has the potential to translate into a mechanistic understanding of risk for mood disorders, which now afflict about one in every 10 young people at any given time, but also the creation of innovative de- velopmentally sensitive interventions. The specific aims are: 1) Determine in healthy adolescents how puberty influences neural activity in and functional connectivity between neural regions supporting attentional control in the context of emotional stimuli; 2) Determine in healthy adolescents the extent to which pubertal influences on reward systems will enhance reward-modulation of attentional control in the context of emotional stimuli. Exploratory analyses will examine pubertal influences on brain structure and how changes in neural indices across puberty relate to changes in levels of mood symptoms. A longitudinal design will be used to disentangle pubety- vs. age-related effects by recruiting groups of males and females matched on age but differing in pubertal status. Levels of sex hormones will be measured to determine individual differences in pubertal maturation. Frontolimbic function will be probed using an fMRI emotional working memory paradigm (with and without incentives) known to recruit prefrontal cortical regions, involved in attentional control, and subcortical limbic regions associated with emotion processing. This approach is innovative because it examines puberty-specific effects on frontolimbic-striatal systems implicated in emotion regulation. The proposed research is significant, because it can lead to the identification of neural markers of risk for mood disorders and inform future intervention studies grounded in knowledge from developmental neuroscience.